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NEPHROLOGY DIALYSIS TRANSPLANTATION 19: 1116-1122 (2004)

Abstract

Background. Autosomal dominant polycystic kidney disease (ADPKD) is genetically heterogeneous disease caused by mutations in at least three different loci. Mutations in the PKD2 gene are responsible for about 15% cases of the disease, based on linkage analysis. PKD2 linked ADPKD is supposed to be milder form of the disease, with a mean age of end-stage renal failure (ESRF) approximately 20 years later than PKD1. Methods. We screened all coding sequences of the PKD2 gene in 115 Czech patients. 52 patients (29 males, 23 females) who reached ESRF after 63 years of age and 10 patients who were not undergoing renal replacement therapy at that age (3 males, 7 females) were selected from dialysis centers from Czech Republic and from Department of Nephrology of General Hospital in Prague. The age 63 years was used as the cutoff value because it is between the age of onset of ESRF for PKD1 and PKD2 published in recent studies. 53 patients (26 males, 27 females) were selected from the PKD families who could be linked either to the PKD1 gene or PKD2 gene according to linkage analysis (without clear information about their clinical course). An affected member from each family was analyzed by heteroduplex analysis (HA) for all 15 coding regions. Samples exhibiting shifted bands on gels were sequenced. Results. We detected twenty two mutations (six new mutations), 14 mutation in 62 patients (23%) with mild clinical course, 8 mutations in 53 families (15%) with possible linkage to both PKD genes. As the detection rate of HA is about 70-80%, we estimate the 18-20% prevalence of PKD2 cases in ADPKD Czech population. We described two cases with severe form of ADPKD and PKD2 mutation. We identified the nonsense mutations in eight patients (36.5%), the frameshifting mutations in twelve patients (54.5%) and two missense mutations (9%). Conclusion. We detected twenty mutations (six new mutations). We established the 18-20% prevalence of PKD2 cases of ADPKD in Czech Republic without known clinical course and 23% prevalence in a group of ADPKD patients with milder clinical course. The mean age of ESRF of PKD2 patients in Czech population was 68.3±4 years (from 64 years to 80 years).. We identified the insertion of a cytosine in exon 1 in six non related Czech patients. This seems to be at least a weak hot spot for mutations of PKD2 gene. We described two PKD2 cases with severe clinical course.